rs144227604

Variant names:

• chr7-72106206-C-T
• rs144227604
• NM_031468.4:c.333G>A

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_031468.4(CALN1):​c.333G>A​(p.Gly111Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000273 in 1,614,042 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0014 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00015 (0 hom.)
• Consequence: CALN1 NM_031468.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.595
• Publications: 0 publications found

Genes affected

CALN1 (HGNC:13248): (calneuron 1) This gene encodes a protein with high similarity to the calcium-binding proteins of the calmodulin family. The encoded protein contains two EF-hand domains and potential calcium-binding sites. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.3).
• BP6: Variant 7-72106206-C-T is Benign according to our data. Variant chr7-72106206-C-T is described in ClinVar as Benign. ClinVar VariationId is 714347.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.595 with no splicing effect.
• BS2: High AC in GnomAd4 at 217 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031468.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CALN1	NM_031468.4	MANE Select	c.333G>A	p.Gly111Gly	synonymous	Exon 4 of 7	NP_113656.2	Q9BXU9-2
	CALN1	NM_001017440.3		c.207G>A	p.Gly69Gly	synonymous	Exon 3 of 6	NP_001017440.1	Q9BXU9-1
	CALN1	NM_001363460.1		c.207G>A	p.Gly69Gly	synonymous	Exon 3 of 6	NP_001350389.1	A4D1Z1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CALN1	ENST00000395275.7	TSL:5 MANE Select	c.333G>A	p.Gly111Gly	synonymous	Exon 4 of 7	ENSP00000378690.2	Q9BXU9-2
	CALN1	ENST00000329008.9	TSL:1	c.207G>A	p.Gly69Gly	synonymous	Exon 3 of 6	ENSP00000332498.5	Q9BXU9-1
	CALN1	ENST00000395276.6	TSL:1	c.207G>A	p.Gly69Gly	synonymous	Exon 4 of 7	ENSP00000378691.2	Q9BXU9-1

Frequencies

GnomAD3 genomes AF: 0.00143 AC: 218 AN: 152112 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00480

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000786

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.000957

GnomAD2 exomes AF: 0.000386 AC: 97 AN: 251274 AF XY: 0.000258

Gnomad AFR exome AF: 0.00492

Gnomad AMR exome AF: 0.000405

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000880

Gnomad OTH exome AF: 0.000326

GnomAD4 exome AF: 0.000153 AC: 224 AN: 1461812 Hom.: 0 Cov.: 31 AF XY: 0.000120 AC XY: 87 AN XY: 727196

African (AFR) AF: 0.00526 AC: 176 AN: 33480

American (AMR) AF: 0.000335 AC: 15 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86246

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53378

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00000540 AC: 6 AN: 1112000

Other (OTH) AF: 0.000447 AC: 27 AN: 60394

GnomAD4 genome AF: 0.00143 AC: 217 AN: 152230 Hom.: 0 Cov.: 31 AF XY: 0.00153 AC XY: 114 AN XY: 74434

African (AFR) AF: 0.00479 AC: 199 AN: 41554

American (AMR) AF: 0.000785 AC: 12 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5140

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68024

Other (OTH) AF: 0.000947 AC: 2 AN: 2112

Alfa AF: 0.000802 Hom.: 0

Bravo AF: 0.00179

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.30
CADD	Benign	9.5
DANN	Benign	0.83
PhyloP100		-0.59

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs144227604; hg19: chr7-71571191; COSMIC: COSV100205324; COSMIC: COSV100205324;